Interaction of spironolactone with rat skin androgen receptor

Abstract

Some characteristics of the dorsal skin cytoplasmic androgen receptor (AR) were studied in male rats. The affinity constant, the binding specificity and the sedimentation profile of the receptor were similar to the rat prostate AR. The measurement of the number of binding sites in various hormonal conditions (deprivation) led to the conclusion that this receptor was largely occupied by endogeneous hormones from gonadal and (or) adrenal sources. Administration of spironolactone or canrenone to 7 day castrated rats was accompanied by a rapid and drastic decrease of available binding sites. This diminution was ascribed to the competitive inhibition of canrenone, the active in vivo metabolite of spironolactone. The antiandrogenic action of spironolactone, at the skin level, is mediated by canrenone which inhibits the formation of specific testosterone and (or) 5.alpha.-dihydrotestosterone receptor complex in cytoplasm and consequently in nuclei. This drug may be useful in the treatment of hirsutism in women.